Stable Microbubbles Research Articles

STABLE MICROBUBBLE TEST IN THE EARLY DIAGNOSIS OF NEWBORN RESPIRATORY DISTRESS SYNDROME

Objective: To analyze the importance of SMT in the early diagnosis of NRDS in newborns (NB) with gestational age between 32 and 37 weeks with respiratory distress. Methodology: observational, cohort study. Data collection occurred in a public hospital in southern Brazil between March 2018 and February 2020. Results: The groups of patients with and without respiratory distress were compared in relation to the number of stable microbubbles. Among the NBs with respiratory distress (RD), 50% presented between 15 and 50 SM/mm² and 50% above 50 SM/mm². On the other hand, 18% of the patients without RD presented between 15 and 50 SM/mm², while 82% presented more than 50 SM/mm², with no significant difference or association. The mothers of NBs with RD received pre-delivery corticosteroid therapy, a protective factor for developing NRDS, not requiring the administration of exogenous surfactant. Conclusion: using the SMT to aid in the diagnosis of NRDS was an effective method since there was no NB with less than 15 SM/mm² and no NB required exogenous surfactant. Certainly, the amount greater than 15 SM/mm² in NB with respiratory distress accuses moderate or severe SDRRN, which does not require administrating exogenous surfactant.

Effect of ambient gas and crystal features on Doppler ultrasound twinkling of pathological mineralizations.

Color Doppler twinkling on kidney stones and other pathological mineralizations is theorized to arise from stable microbubbles, which suggests twinkling will be sensitive to ambient gas. Here, lab-grown cholesterol, calcium phosphate, and uric acid crystals were imaged with ultrasound in water while varying oxygen, carbon dioxide, and nitrogen levels. Twinkling was found to increase on cholesterol in elevated oxygen, cholesterol and calcium phosphate in elevated carbon dioxide, and no crystals in elevated nitrogen. These results support the crevice microbubble theory of twinkling and suggest gases may be varied to enhance twinkling on some mineralizations.

Micro-interface enhanced mass transfer sodium carbonate absorption carbon dioxide reaction

Micro-interface intensified reactor (MIR) can be applied in series/parallel in the absorption of CO2 in industrial gases by Na2CO3 due to the ability to produce large numbers of stable microbubbles. This work focuses on the variation pattern of mass transfer characteristics parameters of the reaction gas in Na2CO3 solution under the influence of different solution properties and operating parameters in the reaction of CO2 absorption by Na2CO3. The mass transfer characteristics parameters include bubble Sauter mean diameter, gas holdup, interfacial area, liquid side mass transfer coefficient, and liquid side volume mass transfer coefficient kLa. The solution properties and operating parameters include Na2CO3 concentration (0.05–2.0 mol·L−1), superficial gas velocity (0.00221–0.01989 m·s−1), superficial liquid velocity (0.00332–0.02984 m·s−1), and ionic strength (1.42456–1.59588 mol·kg−1). And volumetric mass transfer coefficients kLa and superficial reaction rates r of the MIR and the bubble column reactor are compared in the reaction of sodium carbonate absorption of carbon dioxide, and the former shows a greater improvement under different solution properties and operating parameters. The enhanced role of MIR in mass transfer in non-homogeneous reactions is verified and the feasibility of industrial practical applications of MIR is demonstrated.

Enhancing Structural Stability of Oil-Shell Microbubbles via Incorporation of a Gold Nanoparticle Protective Shell for Theranostic Applications

Phospholipid-stabilized microbubbles are utilized as contrast agents in medical ultrasound imaging, and researchers are currently investigating their potential as theranostic agents. Due to the inadequate water solubility and poor stability of numerous new therapeutics, the development of stable microbubbles with the capacity to encapsulate hydrophobic therapeutics is necessary. Herein, we proposed a flow-focusing microfluidic device to generate highly monodispersed, phospholipid-stabilized dual-layer microbubbles for theranostic applications. The stability and microstructural evolution of these microbubbles were investigated by microscopy and machine-learning-assisted segmentation techniques at different phospholipid and gold nanoparticle concentrations. The double-emulsion microbubbles, formed with the combination of phospholipids and gold nanoparticles, developed a protective gold nanoparticle shell that not only acted as a steric barrier against gas diffusion and microbubble coalescence but also alleviated the progressive dewetting instability and the subsequent cascade of coalescence events.

RAPID DIAGNOSIS OF RESPIRATORY DISTRESS SYNDROME BY ORAL ASPIRATE IN PREMATURE NEWBORNS – A PROSPECTIVE COMPARATIVE STUDY

Background and Objectives: Respiratory distress syndrome is common in premature infants; frequency is inversely proportional to gestation and birth weight. RDS is mostly caused by surfactant deciency. For the diagnosis of RDS in newborns, the stable microbubble test on gastric aspirate and amniotic uid has been employed. The major goal of this study was to assess how well the stable microbubble test might predict RDS from oral aspirates of preterm babies. A prospective comparative study was Methodology: done on 73 inborn preterm neonates of AJIMS, Mangalore over the period of 18 months. Neonates with gestation <37weeks were included in the study. Oral sample was collected as soon as baby delivered. Stable microbubble test was done for all the babies, number of stable microbubbles were compared between newborns with RDS and newborns without RDS. Number of stable microbubbles were also compared with requirement of surfactant, use of CPAP and ventilator. The mean number of stable microbubbles i Results: n those with RDS was 17.77 SD ± 6.746 and in those without RDS was 31.14 SD ± 8.26. At a cut-off level of ≤25 microbubbles with Sensitivity 87%, specicity 78.57%, PPV 75% and NPV 89.2%. The ndings of our study suggest that sensitivity of chest x-ray in detecting RDS was 77.4%, specicity 92.86%. The negative and positive predictive value of chest x-ray in detecting RDS were 84.78% and 88.89% respectively. In comparison to Chest X ray in Conclusion: detection of RDS, stable microbubble test was found to be more sensitive at a cut off value of <25 stable microbubbles. However, specicity was found to be better with chest x-ray. Hence, stable microbubble test can be considered as a better screening test for RDS in preterm.

Superiorly Stable Three-Layer Air Microbubbles Generated by Versatile Ethanol-Water Exchange for Contrast-Enhanced Ultrasound Theranostics.

Microbubbles have been widely used as ultrasound contrast agents in clinical diagnosis. Moreover, most current preparation methods for microbubbles are uncontrollable, and the as-obtained microbubbles are unstable in aqueous solution or under ultrasound. Here, we report a strategy to prepare superiorly stable microbubbles with three-layer structures by the ethanol-water exchange. This versatile method can also be applied to prepare different kinds of protein microbubbles with various sizes for advanced biomedical applications. To demonstrate this, the protein air microbubbles are created, which is stable in water for several days with intact structures and exhibits excellent contrast-enhanced ultrasound imaging. Moreover, the protein air microbubbles can also deliver a mass of drugs while maintaining their stable structures, making them a platform for ultrasound imaging-guided drug delivery. The versatile protein air microbubbles have great potential for the design and application of theranostic platforms.

In situ hydrogel capturing nitric oxide microbubbles accelerates the healing of diabetic foot.

Diabetic foot ulcer (DFU) is a devastating complication in diabetes patients, imposing a high risk of amputation and economic burden on patients. Sustained inflammation and angiogenesis hindrance are thought to be two key drivers of the pathogenesis of such ulcers. Nitric oxide (NO) has been proven to accelerate the healing of acute or chronic wounds by modulating inflammation and angiogenesis. However, the use of gas-based therapeutics is difficult for skin wounds. Herein, therapeutic NO gas was first prepared as stable microbubbles, followed by incorporation into a cold Poloxamer-407 (P407) solution. Exposed to the DFU wound, the cold P407 solution would rapidly be transformed into a semisolid hydrogel under body temperature and accordingly capture NO microbubbles. The NO microbubble-captured hydrogel (PNO) was expected to accelerate wound healing in diabetic feet. The NO microbubbles had an average diameter of 0.8±0.4μm, and most of which were captured by the in situ P407 hydrogel. Moreover, the NO microbubbles were evenly distributed inside the hydrogel and kept for a longer time. In addition, the gelling temperature of 30% (w/v) P407 polymer (21°C) was adjusted to 31°C for the PNO gel, which was near the temperature of the skin surface. Rheologic studies showed that the PNO gel had mechanical strength comparable with that of the P407 hydrogel. The cold PNO solution was conveniently sprayed or smeared on the wound of DFU and rapidly gelled. In vivo studies showed that PNO remarkably accelerated wound healing in rats with DFU. Moreover, the sustained inflammation at the DFU wound was largely reversed by PNO, as reflected by the decreased levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and the increased levels of anti-inflammatory cytokines (IL-10, IL-22 and IL-13). Meanwhile, angiogenesis was significantly promoted by PNO, resulting in rich blood perfusion at the DFU wounds. The therapeutic mechanism of PNO was highly associated with polarizing macrophages and maintaining the homeostasis of the extracellular matrix. Collectively, PNO gel may be a promising vehicle of therapeutic NO gas for DFU treatment.

Rich microbubbles modifying the leaching mechanism of aluminum and aluminum nitride of secondary aluminum dross in sodium aluminate solution

An understanding of the mechanisms of reactive Al and AlN in a sodium aluminate solution contributes to the safe and effective utilization of secondary aluminum dross (SAD). This study demonstrates that the slurry temperature increased exponentially with an increase in the SAD dosage. Synergistic kinetic phenomena in the form of a large dosage and high temperature occurred initially in relatively stable microbubbles and later in the slurry. The leaching efficiencies of pure Al and AlN powders were greater than that of Al and AlN in SAD, respectively. Meanwhile, the leaching rate became higher for Al in SAD but lower for AlN in SAD compared to that of pure Al and AlN powder. The AlN particles in SAD were covered by Al(OH)3 precipitated from the saturated solution in the bubbles. As a result, the relatively stable microbubbles with a thick border accelerated the reaction of Al and AlN and produced a saturated solution thereby changing the leaching efficiency and leaching rate of AlN in SAD. The embedded Al and AlN grains in the SAD, relatively stable microbubbles, and the SAD particles covered by Al(OH)3, synergistically changed the leaching mechanism. These results provide further understanding of the reaction mechanism of rich bubbles and facilitate the optimization of the comprehensive utilization of SAD.

Generating Lifetime-Enhanced Microbubbles by Decorating Shells with Silicon Quantum Nano-Dots Using a 3-Series T-Junction Microfluidic Device

Long-term stability of microbubbles is crucial to their effectiveness. Using a new microfluidic device connecting three T-junction channels of 100 μm in series, stable monodisperse SiQD-loaded bovine serum albumin (BSA) protein microbubbles down to 22.8 ± 1.4 μm in diameter were generated. Fluorescence microscopy confirmed the integration of SiQD on the microbubble surface, which retained the same morphology as those without SiQD. The microbubble diameter and stability in air were manipulated through appropriate selection of T-junction numbers, capillary diameter, liquid flow rate, and BSA and SiQD concentrations. A predictive computational model was developed from the experimental data, and the number of T-junctions was incorporated into this model as one of the variables. It was illustrated that the diameter of the monodisperse microbubbles generated can be tailored by combining up to three T-junctions in series, while the operating parameters were kept constant. Computational modeling of microbubble diameter and stability agreed with experimental data. The lifetime of microbubbles increased with increasing T-junction number and higher concentrations of BSA and SiQD. The present research sheds light on a potential new route employing SiQD and triple T-junctions to form stable, monodisperse, multi-layered, and well-characterized protein and quantum dot-loaded protein microbubbles with enhanced stability for the first time.

Combining Ultrasound and Capillary-Embedded T-Junction Microfluidic Devices to Scale Up the Production of Narrow-Sized Microbubbles through Acoustic Fragmentation.

Microbubbles are tiny gas-filled bubbles that have a variety of applications in ultrasound imaging and therapeutic drug delivery. Microbubbles can be synthesized using a number of techniques including sonication, amalgamation, and saline shaking. These approaches can produce highly concentrated microbubble suspensions but offer minimal control over the size and polydispersity of the microbubbles. One of the simplest and effective methods for producing monodisperse microbubbles is capillary-embedded T-junction microfluidic devices, which offer great control over the microbubble size. However, lower production rates (∼200 bubbles/s) and large microbubble sizes (∼300 μm) limit the applicability of such devices for biomedical applications. To overcome the limitations of these technologies, we demonstrate in this work an alternative approach to combine a capillary-embedded T-junction device with ultrasound to enhance the generation of narrow-sized microbubbles in aqueous suspensions. Two T-junction microfluidic devices were connected in parallel and combined with an ultrasonic horn to produce lipid-coated SF6 core microbubbles in the size range of 1-8 μm. The rate of microbubble production was found to increase from 180 microbubbles/s in the absence of ultrasound to (6.5 ± 1.2) × 106 bubble/s in the presence of ultrasound (100% ultrasound amplitude). When stored in a closed environment, the microbubbles were observed to be stable for up to 30 days, with the concentration of the microbubble suspension decreasing from ∼2.81 × 109/mL to ∼2.3 × 106/mL and the size changing from 1.73 ± 0.2 to 1.45 ± 0.3 μm at the end of 30 days. The acoustic response of these microbubbles was examined using broadband attenuation spectroscopy, and flow phantom imaging was performed to determine the ability of these microbubble suspensions to enhance the contrast relative to the surrounding tissue. Overall, this approach of coupling ultrasound with microfluidic parallelization enabled the continuous production of stable microbubbles at high production rates and low polydispersity using simple T-junction devices.

Improved hybrid-shelled perfluorocarbon microdroplets as ultrasound- and laser-activated phase-change platform

HypothesisWe propose significant improvements to perfluorocarbon microdroplets, conferring them colloidal stability, chemical versatility, and size control. Decafluoropentane cores are stabilized by biocompatible interfaces – either a monolayer of the cationic surfactant dimethyldioctadecylammonium bromide (DDAB) or a double shell obtained by adding crosslinked dextran methacrylate as further coating – and functionalised with gold nanoparticles. We hypothesize that this formulation enables dual, acoustic (ADV) and optical (ODV) vaporisation of microdroplets into microbubbles, yielding a versatile “phase-change” theranostic platform. ExperimentsMicrodroplets synthesis is optimized by high-speed homogenization methodology. Functionalisation with gold nanoparticles is achieved by electrostatic decoration. The colloidal suspension is characterised by the concerted use of dynamic light scattering, electrophoresis, and confocal microscopy, to assess microdroplets’ stability. Additional structural details are provided by small-angle X-ray scattering. We analysed the ultrasound- and laser-stimulated transition into microbubbles and characterised their response to ultrasound by acoustic spectroscopy. FindingsHybrid-shelled microdroplets were produced at high density, with narrow diameter distribution (~1 µm). The highly charged surface and the long hydrocarbon tails of DDAB protruding within the core provide high stability. The elastomeric dextran layer at the water interface allows obtaining stable cavitating microbubbles by ADV exhibiting interesting viscoelastic features. The presence of gold nanoparticles unlocks the opto-thermal microdroplet vaporisation.

Enhancing In Vitro Stability of Albumin Microbubbles Produced Using Microfluidic T-Junction Device.

Microfluidics is an efficient technique for continuous synthesis of monodispersed microbubbles. However, microbubbles produced using microfluidic devices possess lower stability due to quick dissolution of core gas when exposed to an aqueous environment. This work aims at generating highly stable monodispersed albumin microbubbles using microfluidic T-junction devices. Microbubble generation was facilitated by an aqueous phase consisting of bovine serum albumin (BSA) as a model protein and nitrogen (N2) gas. Microbubbles were chemically cross-linked using dilute glutaraldehyde (0.75% v/v) solution and thermally cross-linked by collecting microbubbles in hot water maintained at 368 (±2) K. These microbubbles were then subjected to in vitro dissolution in an air-saturated water. Microbubbles cross-linked with a combined treatment of thermal and chemical cross-linking (TC & CC) had longer dissolution time compared to microbubbles chemically cross-linked (CC) alone, thermally cross-linked (TC) alone, and non-cross-linked microbubbles. Circular dichroism (CD) spectroscopy analysis revealed that percent reduction in alpha-helices of BSA was higher for the combined treatment of TC & CC when compared to other treatments. In contrast to non-cross-linked microbubbles where microbubble shell dissolved completely, a significant shell detachment was observed during the final phase of the dissolution for cross-linked microbubbles captured using high speed camera, depending upon the extent of cross-linking of the microbubble shell. SEM micrographs of the microbubble shell revealed the shell thickness of microbubbles treated with TC & CC to be highest compared to only thermally or only chemically cross-linked microbubbles. Comparison of microbubble dissolution data to a mass transfer model showed that shell resistance to gas permeation was highest for microbubbles subjected to a combined treatment of TC & CC.

Ultrasound Responsive Noble Gas Microbubbles for Applications in Image-Guided Gas Delivery.

Noble gases, especially xenon (Xe), have been shown to have antiapoptotic effects in treating hypoxia ischemia related injuries. Currently, in vivo gas delivery is systemic and performed through inhalation, leading to reduced efficacy at the injury site. This report provides a first demonstration of the encapsulation of pure Xe, Ar, or He in phospholipid-coated sub-10 µm microbubbles, without the necessity of stabilizing perfluorocarbon additives. Optimization of shell compositions and preparation techniques show that distearoylphosphatidylcholine (DSPC) with DSPE-PEG5000 can produce stable microbubbles upon shaking, while dibehenoylphosphatidylcholine (DBPC) blended with either DSPE-PEG2000 or DSPE-PEG5000 produces a high yield of microbubbles via a sonication/centrifugation method. Xe and Ar concentrations released into the microbubble suspension headspace are measured using GC-MS, while Xe released directly in solution is detected by the fluorescence quenching of a Xe-sensitive cryptophane molecule. Bubble production is found to be amenable to scale-up while maintaining their size distribution and stability. Excellent ultrasound contrast is observed in a phantom for several minutes under physiological conditions, while an intravenous administration of a bolus of pure Xe microbubbles provides significant contrast in a mouse in pre- and post-lung settings (heart and kidney, respectively), paving the way for image-guided, localized gas delivery for theranostic applications.

The fabrication of protein microbubbles with diverse gas core and the novel exploration on the role of interface introduction in protein crystallization

Recently, microbubbles with diameters ranging from a few to tens of microns have an increasing attractive attention in various applications. For microbubbles, exploring convenient and reliable fabrication approach is crucial, in particular achieving stable microbubbles filled with diverse gas. In this work, the baffled high intensity agitation (BHIA) cell was utilized to generate bovine serum albumin (BSA)-coated microbubbles. The characteristics of generated air-filled microbubbles was explored by adjustment of operating parameters. It was found that the microbubble size mainly depends on employed agitation speed. Microbubbles filled with different gas, such as N2, O2, and CO2, also were successfully obtained and show good stability at room temperature due to the formation of thick and elastic BSA shell. It was interestingly observed that a large number of regular BSA particles scattered around the trajectory of microbubble interfaces by scanning electron microscopy, which was obviously different from the particles formed from BSA solution in absence of microbubbles. The mechanism behind the phenomenon was investigated, and it was found that the abundant gas-liquid interface introduced by microbubbles is responsible for triggering the oriented aggregation of BSA molecules. The founding may reveal a spur significant for the effect of gas-liquid interface on the formation of protein crystals.

Characterizing Hydrogen Microbubble Stiffness Properties Using Atomic Force Microscopy

In the past decades, bubbles have been gaining extensive attentions for their wide range of applications, especially those at the micro-scale. Research on the bubbles’ mechanical properties is necessary for better implementations. Precise measurement of the microbubbles’ mechanical properties (e.g. stiffness and adhesion) relies largely on delicate manipulation technologies in aqueous environment. As a consequence, atomic force microscopy (AFM) has been widely adopted in this field. Bubble stiffness is an important indicator to reflect the stability. Existing studies mainly focused on statistic property of the microbubbles’ stiffness, which may omit delicate specific characteristics of a single microbubble. In this letter, as an instance, AFM-based stiffness measurement of a single hydrogen microbubble has been carried out. The electrochemistry method was adopted to generate stable hydrogen microbubbles. By using force volume mode of a commercial AFM, the temperature-dependent stiffness property of the microbubble was studied. Furthermore, stiffness map of a single microbubble was captured, which shows location-dependent anisotropic characteristic, contradicting the preassumption that stiffness of bubbles should be isotropic. To explain this phenomenon, the contact condition between the AFM tip and the bubble surface is considered as the key reason that induces the anisotropic observation, and a corresponding model is established to verify this hypothesis.

Effect of Temperature on Stability of Lipid Microbubbles

The effect of temperature on stability of lipid microbubble shell containing polyethyleneoxide-40-stearate (PEG40St) as emulsifier was investigated. Microbubbles at 4 °C were subjected to different temperatures up to 48 ºC (down-to-up) and it was found that both the number and the size of microbubbles remained unchanged in the population up to a certain time, so called “onset time”. The onset time was about 6 hrs at 10 °C, 2 hrs at 20 °C and shorter at elevated temperatures, exhibiting an exponential decrease with increasing temperature. Once the onset time was reached, the number of microbubbles started to decrease and the average size of the population started to increase. Observation of single microbubbles on a constant temperature heating stage exhibited that each microbubble had its own onset time, with the smaller microbubbles vanishing earlier than the larger ones. The Langmuir monolayer studies showed that hydration degree of the emulsifier PEG chains decreased with temperature, causing them go through conformational changes and subsequently destabilization of the shell. By subjecting the freshly produced microbubbles directly to the desired temperatures in up-to-down fashion, more stable microbubbles were able to be produced, with their onset time increased 40% at 10 °C to 500% at 38 °C. Overall, the results suggest that the new strategies need to be developed to control the collapse process in the microbubble shell resulting from the conformational changes in the PEG chains of the emulsifier for the design of more stable microbubbles.

Influence of Perfluorohexane-Enriched Atmosphere on Viscoelasticity and Structural Order of Self-Assembled Semifluorinated Alkanes at the Air-Water Interface.

Semifluorinated alkanes FnHm self-assemble into nanometer-sized surface micelles at the air-water interface. In this study, we investigated how an atmosphere enriched with perfluorohexane (PFH) influences the interfacial viscoelasticity and structural order of a monolayer of FnHm by the combination of dilational rheology and grazing-incidence small-angle X-ray scattering (GISAXS). The monolayers behaved predominantly elastic which can be attributed to the strong dipole repulsions of the surface domains. Enrichment of the atmosphere with PFH lead to an increase of the compressibility and a decrease of the elastic modulus without altering the structural ordering of the FnHm molecules into highly correlated nanodomains, suggesting the adsorption of PFH molecules to the free spaces between the domains. The capability of FnHm domains to retain the structural integrity in the presence of PFH gas is promising for the fabrication of stable microbubbles for sonographic imaging.

Etiology of the color Doppler twinkling artifact on kidney stones

Rapid Doppler shifts highlight some kidney stones with a rapid change in color in ultrasound imaging which is called the “twinkling artifact.” Many hypotheses exist to describe the mechanism of twinkling, including the hypothesis that microbubbles are stabilized in crevices on the surface of kidney stones. The objective is to evaluate the distribution of stable microbubbles on kidney stone surfaces with humidity-controlled scanning electron microscopy (ESEM) and determine whether any sub-surface characteristics as assessed with micro-computed tomography (µCT) may contribute to twinkling. A Verasonics® research ultrasound system with the Verasonics L22-14 and Philips/ATL L7-4 and C5-2 transducers quantified twinkling. Results show a correlation between voids within kidney stones and the locations of twinkling on the stone surface. These voids had a calculated free-field Minneart resonant frequency of 3–9 MHz depending on the size. ESEM revealed that surfaces that twinkled had more crevices with radii corresponding to bubbles with a free-field resonant frequency of 3–7 MHz. These results suggest that internal voids and surface crevices contribute to the twinkling artifact on kidney stones.

The effect of crystal chemical composition on the color Doppler ultrasound twinkling artifact

The color Doppler ultrasound twinkling artifact, or localized areas of rapid color shifts, has been used to aid in the diagnosis of kidney stones. Gallstones and some atherosclerotic plaques have also been shown to twinkle, suggesting that crystals, regardless of chemical composition, may harbor the stable microbubbles that are hypothesized to cause twinkling. Here, uric acid, cholesterol, and calcium phosphate crystals, which are often present in sites of pathological biomineralization, were grown in the lab using previously developed techniques and imaged with the Verasonics® research ultrasound system using Philips/ATL P4-2 and Verasonics L22-14 transducers. The magnitude of the Doppler signals was quantified and compared amongst the three crystal chemical compositions. Preliminary results show that all three crystal types displayed twinkling with the strongest magnitude appearing in the cholesterol crystals. These results suggest that twinkling is very sensitive in the presence of crystals regardless of the chemical composition. Future work will explore the use of histotripsy to mechanically fractionate crystals as a novel treatment for pathological biomineralization.The color Doppler ultrasound twinkling artifact, or localized areas of rapid color shifts, has been used to aid in the diagnosis of kidney stones. Gallstones and some atherosclerotic plaques have also been shown to twinkle, suggesting that crystals, regardless of chemical composition, may harbor the stable microbubbles that are hypothesized to cause twinkling. Here, uric acid, cholesterol, and calcium phosphate crystals, which are often present in sites of pathological biomineralization, were grown in the lab using previously developed techniques and imaged with the Verasonics® research ultrasound system using Philips/ATL P4-2 and Verasonics L22-14 transducers. The magnitude of the Doppler signals was quantified and compared amongst the three crystal chemical compositions. Preliminary results show that all three crystal types displayed twinkling with the strongest magnitude appearing in the cholesterol crystals. These results suggest that twinkling is very sensitive in the presence of crystals regardless ...

“Point‐and‐Shoot” Synthesis of Metallic Ring Arrays and Surface‐Enhanced Optical Spectroscopy

AbstractThe realization of optically active structures with direct‐write printing has been challenging, particularly in spatially constrained microfluidic devices which are essential for point‐of‐care (POC) applications. The existing techniques are limited by resolution, accessibility, and multistep fabrication constraints. “Point‐and‐shoot” strategies to achieve site‐specific fabrication of optically active Ag rings and on‐demand targeted surface‐enhanced optical spectroscopy are reported. Stable microbubbles over an Au nanoisland (AuNI) substrate are generated using a continuous‐wave laser at low power (≈0.5 mW µm−2). Analytical modeling of bubble generation process substantiates the evolution of ring morphology and its power dependence. The tunable Ag rings exhibit surface plasmon resonances in the mid‐IR regime from 3.8 to 4.6 µm, while the AuNI shows visible region response. The Ag ring over the AuNI imparts intensified surface‐enhanced Raman spectroscopy (SERS) activity owing to amplified hot spots at Ag ring/AuNI interface. As an example, SERS and surface‐enhanced infrared spectroscopy of rhodamine 6G, crystal violet, and 2,4,6‐trinitrotoluene molecules, respectively, are demonstrated. The applicability of this technique to perform in situ fabrication and SERS sensing in microfluidic channels is shown. Using a simple in situ approach toward optically active structures, our technique can synergize multiple surface‐enhanced optical spectroscopies to facilitate POC applications.